Radial and trans-endocardial delivery catheter

ABSTRACT

A needle-injection catheter includes a catheter body having a distal end, a proximal end, a stiff proximal portion, a flexible distal portion, and a delivery lumen extending therethrough. In a first embodiment, a straight injection needle extends coaxially from a distal tip of the flexible portion of the catheter body, and a plurality of penetration limiting elements positioned circumferentially about a base of the straight injection needle and configured to fold radially inwardly against a shaft of the needle when constrained in a tubular lumen and to extend radially outwardly when unconstrained. In a second embodiment, a helical needle extends from the distal tip of the flexible portion of the catheter body. The helical needle has at least one helical delivery lumen connected to receive an injectable substance from the delivery lumen of the catheter body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/884,834 (Attorney Docket No. 29181-706.101), filed Sep. 30, 2013, theentire content of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods and systems.More particularly, the present invention relates to medical methods andsystems suitable for substance delivery to the heart via a radial arteryand for the intracardiac delivery of cellular aggregates and otheragglomerated materials.

Currently, local biotherapeutic delivery to the heart is under clinicalinvestigation for the treatment of acute myocardial infarction, chronicmyocardial ischemia, ischemic heart failure, and nonischemic heartfailure. The leading paradigm of intramyocardial delivery istrans-endocardial delivery.

Currently available delivery systems include the Myostar® catheter,manufactured by Johnson and Johnson Biological Delivery Systems, DiamondBar, Calif., and the BioCardia® Helical Infusion System, manufactured byBioCardia, Inc., San Carlos, Calif., the assignee of the presentinvention. Both these systems utilize an 8 French introducer placedthrough a femoral artery. Both systems have flexible distal portionsthat are deflectable (steerable) from a proximal handle location, andthe BioCardia system includes a centrally located catheter that may beadvanced from the introducer to extend to the heart wall, providingimproved access for the operator.

Typically, it is desirable to use the smallest puncture site andsmallest equipment that meets the requirements of an intervention. Thesmaller the puncture site, the easier it is for the entry point to healwithout complications and the lower the requirement for closure devices.This can be an enormous cost and morbidity reduction for a particularinterventional procedure.

Smaller devices which enable the vasculature to be accessed from theradial artery of the arm (as opposed to the femoral artery in the groin)have enormous advantages from a cost perspective, as the patient isambulatory immediately after a procedure. Reducing the amount of time apatient has to spend on a gurney or in a bed recovering has additionalpatient quality of life advantages in addition to the economicadvantages of reduced hospital time. Radial artery access requiressmaller equipment as has been detailed in the literature extensively. 7Fguides and 6F sheaths (one French (Fr) equals 0.33mm) are the largestdevices that are recommended for such procedures with the outcomesimproving as smaller guides and sheaths are used. Whole Journal issues,Such as Cardiac Interventions Today April 2011, Volume 5, No 2, havebeen dedicated to radial access for procedures and are herebyincorporated by reference. The diameter of the radial artery is suchthat for 95% of all patients have a radial artery greater than 2.2 mm indiameter and can accommodate a 5 French sheath (typical outer diameterof 6.5French) or a 6.5 French guide, 60% have a radial artery greaterthan 2.6 mm in diameter and can accommodate a 6 French sheath (outerdiameter 7.5 French) or a 7.5 French guide, 40% have a radial arterygreater than 2.95 mm which can accommodate a 7 French sheath (outerdiameter 8.5 French) or an 8.5 French guide, and only 20% have a radialartery that is greater than 3.3 mm in diameter which can accommodate an8F sheath (outer diameter 9.5 French) or a 9.5 French guide. Saito S etal Catheter Cardiovas Interve 1999;46:173-178. Typically the sheath sizeirefers to the size of the guide catheter that will fit through it.

A particular difficulty with trans-radial access is providing a guidecatheter that can be advanced straight over a guide wire in anatraumatic fashion through the vasculature with a small profile andwhich can be used to guide a trans-endocardial delivery catheter acrosssmall diameter across bends with angles greater than 70 degrees (andpreferably 90 degrees or even greater) from the axis of the catheterwithin the heart while minimizing the potential for damaging thevasculature during advancement to the heart and perforating the heartdue to the small diameter of the catheter shaft and the stiffness of thedistal region of the catheter.

In some cases, “sheathless” guide catheters can be used without a sheathso that a larger portion of patients may be treated. The use of 5.5F or6.5F sheathless guide catheters can provide a smaller pathway throughthe radial artery by eliminating the use of a sheath.

Once in the heart, stem cells and other therapeutic substances may betrans-endocardially injected using straight, helical or other injectionneedles. Helical needles have typically had small bores while the boresof straight needles have frequently been larger. Larger, straightneedles have usually been used for delivering large agents such as stemand other cells, cellular aggregates, microspheres, extra cellularmatrix (ECM) slurries with effective diameters as large as 80um and150um, particles, and other high viscosity therapeutic agents such ascardiospheres with diameters of 60 to 150 um, and the like. Helical andother small bore needles will typically have difficulty passing suchlarge agents even when the internal diameter is larger than the agents.This is particularly true of aggregated agents which can result in anincrease in viscosity that inhibits delivery. While straight, large boreneedles are capable of delivering such agents, after injection the stemcells and other large, aggregated substances will often be ejected backinto the heart chamber upon contraction of the myocardium, resulting inthe loss of the injectable material as well as a risk of embolism in thecase of larger agglomerates and particles.

For these reasons, it would be desirable to provide improved systems andmethods for the intracardiac delivery of cells, drugs, and othertherapeutic agents. It would be particularly desirable to provideimproved systems and methods for facilitating introduction ofneedle-based delivery catheters via a radial artery approach, where suchsystems preferably include a distal perforation protection system with aminimum space requirement, which is passive and operates without activeactuation, and which provides for robust perforation protectioncapabilities. It would be further desirable to provide improved systemsand methods for using needle-based delivery catheters for deliveringcells, drugs, and other therapeutic agents with a reduced risk of lossof the injected material back into the heart chamber as a result ofheart contraction. At least some of these objectives will be met by theinventions described below.

2. Description of the Background Art

Recently steerable guides and steerable sheaths have been developed thatenable significant advantages for trans-endocardial delivery and othercardiovascular procedures. See U.S. Pat. Nos. 7,840,261, 7,402,151, andU.S. Published Application Nos. 2012/0123327 and 2008/0287918, the fulldisclosures of which are hereby incorporated by reference. Steerableguides and sheaths typically have a wall thickness that is 1 French (OneFrench (Fr) equals 0.33 mm) and standard fixed guides and sheathstypically have a wall thickness of approximately 0.5 Fr.

US Patent Application No. 2012/0123327 (Miller) describes how a 5 Fr or6 Fr steerable sheath can be used to enter the heart from a radialartery using a guide catheter with a flexible distal end, such as theBioCardia Helical Infusion System. For such a system, a 5F steerablesheath would have an internal diameter of 5.5French and an outerdiameter of just over 2.2 mm and would easily pass the 5.2French HelicalInfusion Catheter System (BioCardia, Inc.) and operate substantially asa transradial steerable sheath for trans-endocardial delivery using theHelical Infusion System and would enable a steerable trans-endocardialdelivery platform useful in close to 95% of all patients.

Published U.S. Patent Application Nos. 2007/0005018 and 2010/0168713each discuss the potential advantages of transradial access fortrans-endocardial delivery.

Penetration limiter devices on the end of the trans-endocardial deliverycatheters are known, such as that described by Eclipse SurgicalTechnologies in U.S. Pat. No. 6,322,548. These systems are passivesystems but consume real estate in the distal end of the catheter andrequire a distal catheter shaft construction that would preventtransradial access because of size. U.S. Pat. Nos. 7,803,136; 8,361,039;and 8,414,558 also describe distal protection mechanisms for straightneedle trans-endocardial delivery systems. These all require an activedeployment mechanism which increase the profile of the distal regionsand limit the space for advanced therapeutic lumen design such as theinclusion of a contrast port and lumen to discharge at the base of thepenetrating element to confirm engagement, to use a large bore helicalneedle which has importance for the delivery of agents of higherviscosity or which are larger or have a potential to aggregate, and touse a two lumen penetrating element. Cardiac Interventions Today April2011, Volume 5, No 2 and Saito S et al Catheter Cardiovas Interve1999;46:173-178 have been described above.

SUMMARY OF THE INVENTION

According to the present invention, methods and systems are provided forintracardiac, trans-endocardial infusion of various materials includingdrugs, cells, and in particular large cellular aggregations and otherparticulate substances. Many of the methods and systems are particularlysuited for radial artery access but can rely on femoral artery access aswell. The systems of the present invention may include multipleinterchangeable components such as introducer sheaths, preformed orpre-shaped guide catheters, steerable or deflectable guide catheters,preformed sheathless guide catheters, steerable sheaths or sheathguides, and sheathless steerable sheaths or sheath guides. Each of thevariety of guide catheters may be used for the advancement of multipletypes of delivery catheters, for example having helical needles,straight needles, coaxial helical needles, coaxial straight needles,double barrel helical needles, double barrel curved needles, doublebarrel straight needles, large bore straight needles, large bore curvedneedles, large bore helical needles, and the like. The delivery cathetermay also include contrast lumens that discharges at the base of theneedle or other penetrating element. These catheter systems may beconfigured for fluoroscopic navigation, electrical impedence navigation,electromagnetic navigation using real time magnetic resonance imaging,three-dimensional echo navigation, as well as fusion imaging systemsthat can bring MRI, CT, or echo data and merge it with the fluoroscopicimages. Further these delivery systems have potential to enable a broadvariety of diagnostic and therapeutic agent delivery some embodimentswhich will be disclosed as the inventive elements of the delivery systemenables these novel therapeutic options.

In a first aspect, the present invention provides methods forintroducing needle injection catheters into a heart chamber via a radialartery approach. Such methods comprise advancing a guide catheterthrough the radial artery (and the intervening arterial vasculature) andinto a targeted heart chamber. The catheter will usually enter the rightor left ventricle from the right side of the heart but may be furtheradvanced transeptally within the heart to reach the left ventricle fromthe right side of the heart or other chambers. The guide catheter ispositioned to align a distal tip of the guide catheter with a targetlocation on an endocardial wall of the heart chamber. A needle-injectioncatheter is advanced through a lumen of the guide catheter so that astraight needle projecting coaxially from a distal tip of the needleinjection catheter emerges from the distal tip and penetrates theendocardial wall to position an injection port at the tip of the needlein the myocardium. A plurality of penetration limiting elements remainconstrained within the guide catheter until the straight needle emergesfrom the distal tip at which point the elements self-deploy radiallyoutwardly from a base of the needle, typically resiliently deploying asa result of their own spring-force upon the release of constraint, tolimit the penetration of the needle into the myocardium in order toreduce the risk of perforation of the endocardial wall.

In exemplary embodiments, positioning may comprise rotating and/oraxially translating a guide catheter having a pre-shaped deflection atits distal end. In alternative exemplary embodiments, positioning maycomprise deflecting or “steering” the distal tip of the guide catheterwhile the guide catheter is in the heart chamber. In all cases, theguide catheter will usually be introduced over a guidewire which hasbeen previously placed from the radial artery to the heart chamber in aconventional manner.

In further exemplary embodiments, advancing the needle-injectioncatheter may comprise constraining the penetration limiting elements inan introduce sleeve. A distal end of the sleeve is engaged against aproximal hub of the guide catheter, and a distal end of theneedle-injection catheter is advanced into a proximal portion of theguide catheter while the penetration limiting elements remainconstrained.

In still further exemplary embodiments, the penetration limitingelements may comprise resilient petals which have bases attached to thecatheter body at the base of the straight needle. The petals may beshaped to curve outwardly from the catheter body when unconstrained. Thepetals may wire loops folded in a continuous length of a shape memorywire, and a platinum wire may be wound over the shape memory wire toprovide radiopacity. Alternatively, the petals may comprise solid leavesor other structures which overlap when folded inwardly against theneedle shaft. Typically, in all such embodiments, the catheter includesfrom two to six petals, most typically being three.

In a second aspect, the present invention provides a needle-injectioncatheter comprising a catheter body having a distal end, a proximal end,a stiff proximal portion, a flexible distal portion, and a deliverylumen extending therethrough. By stiff, it is meant that the proximalportion of the catheter body will have sufficient column strength andpushability to be advanced through relatively non-tortuous regions ofthe vasculature and in particular from the radial artery to the heart.By flexible, it is meant that the distal portion will be able to beadvanced across small radius curves to allow positioning within theheart chamber and through pre-shaped or deflected regions of the guidecatheter. The catheter further includes a straight injection needleextending coaxially from a distal tip of the flexible portion of thecatheter body. A plurality of penetration limiting elements arepositioned circumferentially about a base of the straight injectionneedle and are configured to fold radially inwardly against a shaft ofthe needle when constrained in a tubular lumen and to extend radiallyoutwardly when unconstrained.

The penetration limiting elements of the needle-injection catheters maycomprise resilient petals which have bases attached to the catheter bodyat the base of the straight needle. The petals may be shaped to curveoutwardly from the catheter body when unconstrained. The petals may wireloops folded in a continuous length of a shape memory wire, and aplatinum wire may be wound over the shape memory wire to provideradiopacity. Alternatively, the petals may comprise solid leaves orother structures which overlap when folded inwardly against the needleshaft. Typically, in all such embodiments, the catheter includes fromtwo to six petals, most typically being three.

In exemplary embodiments, the stiff proximal portions of the catheterbodies of the needle-injection catheters may comprise a braidedpolymeric tube and the flexible distal portions may comprise a helicalmetal coil. The catheter body will typically have a first lumen fordelivering an injectable composition to the needle and a second lumenfor delivery of a contrast agent to the base of the needle. Theneedle-injection catheters may further comprise a handle or hub(referred to collectively as handles) on the proximal end of thecatheter body, where the handle may include valves, luers, and otherfillings and components as needed for connection to sources of materialto be delivered, contrast agents, guidewires, and the like. The catheterbody will preferably be configured to be delivered through a 6.5 Fr orsmaller guide catheter.

In further embodiments of the present invention, a catheter systemcomprises a needle-injection catheter as described above in combinationwith a guide catheter having a lumen configured to receive theneedle-injection catheter and to radially constrain the plurality ofpenetration limiting elements when the needle-injection catheter istherein. The guide catheter of such a system may have a pre-shaped bendnear its distal end so that the guide catheter can be rotated to alignthe distal end with a target location on an endocardial wall when theguide catheter is in a heart chamber. Alternatively, the guide cathetermay have a deflectable (also referred to as steerable) distal end toallow aligning the distal end with a target location on an endocardialwall when the guide catheter is in a heart chamber.

In a third aspect, the present invention provides a large-bore needleinjection catheter comprising a catheter body having a distal end, aproximal end, and a delivery lumen therethrough. A helical needleextends from the distal end of the catheter body and has at least onehelical delivery lumen connected to receive an injectable substance fromthe delivery lumen of the catheter body. The delivery lumen and the atleast one helical lumen are sufficiently large to permit the passage andinjection of drugs or biological materials having a mean diameter of atleast 100 μm. The catheter body delivery lumen usually has a diameter ofat least 0.50 mm, typically being 0.71 mm in its major non circularaxis, and the helical lumen usually has a diameter of at least 0.2 mm,typically being about 0.43 mm

In specific embodiments, the catheter body has at least one lumen inaddition to the delivery lumen and the helical needle has at least twohelical delivery lumens with one connected to at least the each of thecatheter body lumens. The catheter body may comprises a stiff proximalportion and a flexible distal portion, as described above, wherein thestiff proximal portion of the catheter body may comprise a braidedpolymeric tube and the flexible distal portion of the catheter body maycomprise a helical metal coil. The catheter body may include a firstlumen and optionally a second for delivery of an injectable compositionto the needle and further optionally a second or third second lumen fordelivery of a contrast agent to the base of the needle, and a handle maybe disposed on the proximal end of the catheter body.

In further embodiments of the present invention, a catheter systemcomprises a large-bore catheter as described above in combination with aguide catheter having a lumen configured to receive the large-borecatheter. The guide catheter of such a system may have a pre-shaped bendnear its distal end so that the guide catheter can be rotated to alignthe distal end with a target location on an endocardial wall when theguide catheter is in a heart chamber. Alternatively, the guide cathetermay have a deflectable (also referred to as steerable) distal end toallow aligning the distal end with a target location on an endocardialwall when the guide catheter is in a heart chamber.

In a fourth aspect of the present invention, a method for delivering aparticulate material into an endocardial wall of a heart chamber of abeating heart comprises intravascularly introducing a large bore needleinjection catheter having a helical needle into a heart chamber.Particulate materials that may be delivered include cells, stem cells,stem cell aggregates, and any other therapeutic or diagnostic substanceswhich may present a risk of embolism if accidentally released into aheart chamber when injected, particularly as a result of being extrudedor otherwise expelled from the injection site as a result of thecontraction of the myocardium as the heart beats. The helical needle ofthe large bore needle injection catheter is advanced into an endocardialwall of the heart chamber so that a port on the needle lies near aninterior end of a helical tissue tract formed by the needle. Theparticulate material, typically having a mean particle diameter of atleast 100 μm, is injected through the needle into the interior end ofthe helical tissue tract. Flow back of the injected material through thehelical tissue tract is inhibited in the helical shape of the tract evenafter the helical needle is withdrawn.

In specific embodiments of the particulate delivery methods, thecatheter will have a catheter body with a delivery lumen having adiameter of at least 0.50 mm, preferably being in the range from 0.50 mmto 0.80 mm The helical needle will usually have a helical lumen with adiameter of at least 0.2 mm, preferably being in the range from 0.21 mmto 0.56 mm The catheter body delivery lumen usually has a diameter of atleast 0.50 mm, typically being 0.71 mm in its major non circular axis,and the helical lumen usually has a diameter of at least 0.2 mm,typically being about 0.43 mm The catheter body typically has at leastone lumen in addition to the delivery lumen, and the helical needletypically has at least two helical delivery lumens with one connected toat least the each of the catheter body lumens.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 illustrate prior art guide and delivery catheters that maybe used in certain implementations of the present invention.

FIGS. 3A and 3B illustrate helical delivery catheter implementations ofthe present invention.

FIGS. 4A and 4B illustrate a needle-injection catheter having a straightinjection needle surrounded at its base by penetration limiting elementsaccording to the present invention being advanced from a guide catheter.

FIG. 5 illustrates the distal tip of a needle-injection catheter havinga straight injection needle according to the present invention.

FIGS. 6A through 6E illustrate retraction of a needle-injection catheterhaving a straight injection needle surrounded at its base by penetrationlimiting elements into a guide catheter according to the presentinvention.

FIG. 7 illustrates an exemplary delivery catheter having two lumens anda handle assembly.

FIGS. 8A-1 through 8F-6 illustrate design and fabrication detail of aneedle-injection catheter having a straight injection needle surroundedat its base by penetration limiting elements according to the presentinvention.

FIG. 9 is a cross sectional view of a handle assembly for aneedle-injection catheter according to the present invention.

FIGS. 10 through 12B show of a distal tip of a three lumen needleinjection catheter having a two lumen helical injection needle.

FIGS. 13A and 13B shows design and fabrication details of a tri-lumencatheter body configuration.

FIGS. 14A through 14C show the electrical connections of the deliverycatheter in more detail.

FIG. 15 shows the internal configuration of a handle assembly for thehelical needle delivery catheter of the present invention.

FIGS. 16 and 17 show design and fabrication details for a large borehelical needle for the delivery catheters of the present invention.

FIGS. 18A through 18C illustrate an alternate design for a penetrationlimit which can provide distal perforation protection utilizing existingballoon technology when engaging heart tissue during trans-endocardialtherapy delivery.

FIG. 19 shows an assembled system including a deflectable tip guidecatheter having a valve, a syringe attached to a side port of the valve,a helical needle delivery catheter, a syringe attached a therapeuticport of the valve, and a syringe attached to the contrast port.

FIG. 20 illustrates a helical needle injection catheter including ahelical needle, a flexible distal element, a braided shaft, two-partstrain relief, a handle, a therapeutic port, and a contrast port.

FIGS. 21A through 21D show a helical needle formed by wrapping ahypotube onto a mandrel which supports the sides of the tube to reducedeformation (ovalization).

FIG. 22 shows an alternative design for terminating the contrast andtherapeutic lumens utilizes in a “Y” adapter or other handle.

In this patent application we will disclose inventive elements of eachof these, but their usage is in no way limited to the other elements inthis application.

DESCRIPTION OF THE INVENTION

FIG. 1 (Prior Art) shows a preformed 6F Hockey Stick (HS) 90 cm guidecatheter 100, such as the ConcierGE® Guiding Catheter, available fromMerit Medical Systems, Inc., which is advanced straight or over either adilator or a guide wire from either the femoral or radial artery.Because the distal segment is highly flexible, the guide catheter may besafely advanced across the aortic valve into the left ventricle. Theguide catheter 100 may be advanced into a femoral artery using anycommercially available 6 Fr sheath. For radial access, a longer 25 cmsheath such as the Boston Scientific Super Sheath Catalog 16037-06B ispreferred to avoid complications with radial artery spasm which occursfrequently in patients.

FIG. 2 (Prior Art) shows the preformed 6 Fr HS 90 cm guide catheter 100after a central straightening element, such as a dilator or wire, isremoved and a trans-endocardial infusion catheter 200 with a highlyflexible distal segment 202 with a length of at least 6 to 10 cm whichreaches beyond the end of the guide catheter between 3.5 cm and 7 cm isinserted. Here the penetrating element is a helical needle 204 which mayreadily be rotated within the fixed guide and advanced in order toengage the catheter into the heart tissue. The highly flexible distalsegment 202 on the trans-endocardial infusion catheter 200 does notstraighten the highly flexible guide portion on the 6 Fr guide catheterenabling one to advance and rotate the fixed guide and then extend thehelical needle 204 to the ventricular wall with the trans-endocardialdelivery system to penetrate tissue and accomplish therapeutic ordiagnostic delivery. The preformed guide shape will typically bend atleast 90 degrees as there will be some slight straightening as thetrans-endocardial infusion catheter is inserted due to the need for theguide distal end to be flexible. In FIG. 2, the trans-endocardialinfusion catheter 200 is a BioCardia® helical needle model 953L catheterwhere the highly flexible region comprises a multifilar coil design butother flexible segments can be used in the present invention, e.g. theflexible segment could be made from an etched stainless steel tube suchas shown in U.S. Pat. Nos. 5,228,441; 5,243,167; 5,322,064; 5,329,923;5,334,145; 5,454,787; 5,477,856; and 5,685,868, or form a wound ribbonstructure. The bending rigidity of such coil designs can be readilycalculated by following validated closed form derivations for suchcomplex geometries, as taught for example in Meagher, J., Altman, P.:Stresses from Flexure in Composite Helical Implantable Leads, MedicalEngineering and Physics, Vol. 19, No. 7, pp 668-673, 1997.

Penetrating elements in different aspects of the present invention canbe straight needles, curved needles, multi-pronged needles, and thelike, as well being helical needles. As the pre-shaped catheter guidecatheters used in the methods and systems of the present invention maybe axially advanced and retracted and rotated in the left ventricle, astatic sheath will typically be placed in the first 25 cm of the radialartery to reduce the impact of radial artery spasm on the procedure aswell as the viability of the radial artery at the end of this procedure.A long 6F sheath may also be used with a 6 Fr guide to minimize thepotential for a spasm to bind the inserted catheter and preventcompletion of the procedure.

In some embodiments, a 25 cm 6 Fr introducer sheath and a 110 cmpreformed 6 Fr guide catheter with a preformed 100 degree hockey stickangle are used to advance a 5.2 Fr trans-endocardial delivery catheterwith a penetrating element mounted on the end of a highly flexible coil.These catheters may have two lumens which travel to the distal end, oneof which discharges at the base of the penetrating element and one whichpasses through the penetrating element to discharge into the tissuepenetrated, Further, this catheter system in its preferred embodimenthas a helical needle at its distal tip, eliminating the need forperforation protection device. Clearly, eliminating the need for the 25m 6 Fr sheath by providing a lubricious coating and enabling the 110 cmguide to be used as a sheathless guide enables the system to be used inan additional 35% of the population, and is the preferred embodiment forpatients with smaller radial arteries.

Alternative systems may utilize a steerable 6 Fr guide catheter with anouter diameter set to accommodate the 6 Fr sheath (6.4 Fr or smaller)and an inner diameter selected to accommodate a 4 Fr infusion catheterwith an internal diameter of 3.9 Fr to 4.4 Fr. Such steerable guidecatheters are commercially available, and a suitable steerable guidecatheter is the Universal Deflectable Guide Catheter model #1066,manufactured by BioCardia, Inc., which has a 4.25 Fr internal lumen anda 6 French outer lumen. This approach has the same procedural advantagesas the first embodiment disclosed here, but also benefits from theability to deflect the distal end of the guide providing enhancedcontrol options and also the ability to have greater back up supportwithin the ventricle. This system may also be used with a 25 cm radialaccess sheath, but it is challenged by the ability to pass a largerdiameter helical needle and thus a straight needle system with a passiveperforation protection system is desired which will be described.

An alternative steerable guide catheter suitable in certain embodimentsof the present invention is disclosed in US Patent Publication No.2012/0123327, the full disclosure of which is incorporated herein byreference. This guide catheter allows entry with a 5 French steerablesheath (outer diameter 7.5 French) without an introducer sheath.Although there is added risk of radial artery spasm associated with themanipulation of the device within the artery, its steerable nature maysignificantly reduce the manipulations relative to that of a 6 Frsheathless fixed guide which has a 7 Fr outer diameter. Both thissheathless guide and this steerable sheath system would benefit from alubricious coating along the full length of the catheter shaft. Thepotential to use larger steerable sheaths for the procedure toaccommodate larger catheters for trans-endocardial delivery which havedifferent fluid delivery, electrical mapping, ultrasound sensing,electromagnetic positioning, and other such well understood geometricrequirements may be performed with the caveat that the larger thecatheter the more risk to the radial artery may result. Currently,tri-lumen fluid management with bipolar sensing, as disclosed in U.S.Pat. No. 7,736,346, has been realized in a 5.2 Fr envelope which is 5 Frsheath compatible.

FIGS. 3A and 3B shows the distal end of two trans-endocardial deliverycatheters, each having two lumens: one lumen which is used for thedelivery of contrast media and terminates at the base of the helicalneedle and one which goes all the way to the distal end of the helicalneedle. These needles are formed with a winding fixture that controlspitch and which has channel width specified to prevent flattening orexcess “ovalization” (an unintended deformation of the cross-sectionfrom a circular geometry to an oval or similar non-circular geometry) ofthe circular needle cross-section. Needles are made from 304 stainlesssteel although other materials can also work. In attaching the helicalneedles to the distal end of the catheter the needles are bonded intothe dual lumen internal tubing that is covered with the distalmultifilar coil, a mandrel is inserted into the contrast discharge lumento protect its patency, and the helix is embedded in an epoxy resin,such as Loctite M-31CL where the needle is firmly secured to the distalhighly flexible coil. The smaller diameter helical needle has aninternal diameter of 0.008 inches and the larger diameter Helix has aninternal diameter of 0.022 inches.

FIGS. 4A and 4B show the distal end of a straight needletrans-endocardial catheter 402 system including a delivery catheter 404that has a passive perforation protection system comprising a plurality(three) protective petals 406 surrounding the base of a straightinjection needle 408. FIG. 4A shows the system as it is being deployed,and FIG. 4B shows it as it fully deployed. The systems of the presentinvention includes the catheter of the present invention in combinationwith a guide catheter which could be anyone of a variety of conventionalsteerable or fixed guide catheters having a 5.2 Fr lumen or, in somecases a 4 Fr lumen. The system may optionally further include anintroducer sleeve 817 c, as shown FIG. 8E, that may be a thin-walledslit tube of roughly three to ten centimeters in length that is advancedover the proximal shaft of the needle injection catheter to retractperforation protection device within a lumen of the sleeve. The cathetercan then be advanced from the introducer sleeve into the guide catheterwhich will be used to deliver catheter after the introducer sleeve isremoved.

FIG. 5 shows the distal end of a trans-endocardial delivery system thatis compatible with a 5.5 Fr lumen catheter introducer system 500 inwhich a straight needle 504 is mounted on the distal end of a flexibledistal region 511 of a catheter body or shaft. A contrast port 510 isdisposed at a base of petals 506 which are attached at a distal end ofthe region 511. The straight needle 504 may be a 27 Gage regular wallneedle with a 0.008″ inch lumen, and a 0.016″ outer diameter and anexposed length of 0.160, 0.240, or 0.320. Tip 502 of needle 504preferably has three facets, as shown, but could alternatively have oneor two facets The penetration-limiting petals 506 may be formed fromNitinol® wire 0.0035 inches in diameter which has been served or coveredwith a coil of single filar 0.0015″ diameter platinum iridium (Pt/Ir)90/10) wire over the top for radiopacity. The flexible region of thecatheter may be formed from five filar 0.008″ wire coil 511 with anouter diameter of 0.063″ with a pitch of 0.046″ which extends tencentimeters from the more rigid catheter shaft. A dual lumen PEBAX 55Dpolymer tubing (not shown in FIG. 5) typically extends most or all ofthe length of the catheter. The base of the straight needle penetratingelement 508 is inserted into and bonded to one of two lumens of the duallumen tube. The stem or base of the penetration limiting/perforationprotection structure is inserted 510 into the pentafilar coil 511 butwill typically leave one of the internal lumens open to discharge acontrast medium when needed.

The penetration limiting/perforation protection device can beimplemented in a number of ways. In a preferred embodiment, a monolithicstructure includes a plurality of petals which are partially orcompletely covered with the Pt/Ir wire coil. The wire coveringfacilitates assembly and improves longitudinal and radial spacingconsistency. The covering may also enhance security of attachment.Assembly is performed by straightening the superelastic wire (which ispreformed or set to have the three dimensional petal geometryillustrated herein), and the Pt/Ir coil is advanced over thestraightened wire., The petal wire is then allowed to resume its relaxedmulti-petal shape, and the penetration limiting/peroration protectionstructure is bonded with epoxy into the distal end of the catheter bodyor shaft as noted previously. Additionally or alternatively, thepenetration limiting/perforation protection structure may also beattached using braze, solder, or by welding to the needle and/or thedistal coil.

Other embodiments include the use of distinct parts for each petal in aplurality of petals. Combinations of these are also possible, i.e. twopetals in one monolithic structure and two petals in another monolithicstructure, resulting in a four petal configuration, etc. Further morelimited embodiments in which only one petal deploys from the catheter onone side.

The number of petals or leaflets is significant as it determines thenumber of individual wires that must anchored. Fewer leaflets thusoccupy less of the available space inside the catheter but can result inthicker elements. Since bending stiffness tends to be a third orderfactor on diameter, doubling the diameter gives 8 times the stiffness.Thus anticipated that three loops allows more stiffness (thus resistanceto puncture) than four, and perhaps more stable a geometry than twoloops. The preferred embodiment has three loops but this should notlimit the invention disclosed. The Nitinol® wire can also be selectedfrom a range of sizes, typically 0.002 to 0.005 inches in diameter.

Apparent Cross Sectional Area Relates to Puncture Resistance: In thecontext of perforation protection, the element of interest is the distalend of the main catheter body and not the “penetrating element” orneedle. The force required to cause myocardial perforation/puncture isrelated to the presented cross sectional area of the tip of thecatheter. The wire loop elements disclosed in this applicationeffectively increase the apparent surface area of the distal end of thecatheter body, thus increasing the force which would be required tocause myocardial perforation.

Variable stiffness of the loops: Since the root of each loop or petalnear the distal end of the catheter body is the portion of theloop/petal which is the most resistant to being bent backwards (shortestlever arm to cause the bending), it is the most important to creatingpuncture resistance, and could be made stiffer than the portions of theloop further from the catheter tip, making the system more atraumatic,or more sensitive to contact with fine structures within the heart. FIG.6A through 6E show exemplary loop/petal structures which are suitable asthe penetration limiting/perforation protection elements of the presentinvention and which readily collapses when deployed from or retractedinto the distal end of a guide catheter. FIGS. 6A through 6Especifically show the penetration limiting/perforation protection systemas the delivery catheter is being retracted back into the guidecatheter: FIG. 6A shows the distal region 511 of the infusion catheterextended from a guide catheter 601 with protective petals or leaflets506 at full deployment. FIG. 6B shows the leaflets or petals 506 fullydeployed just before entering the guide catheter 601 as the deliverycatheter is retracted into the guide catheter 601, FIG. 6C shows theleaflets or petals 506 starting to collapse around the needle 502 andinto the guide catheter 601, FIG. 6D show the leaflets or petals 506just prior to full capture by the guide catheter 601. FIG. 6E shows theperforation protection system completely retracted and barely visiblethrough the distal port of the guide catheter 601. This final positionis referred to as the “garaged” state, when the delivery catheter isprotected within the guide and the guide can be manipulated to targetspecific region within the ventricle. This protection device more thandoubles the force to penetrate the heart tissue with a given 5 Frenchstraight needle catheter system. “Flower petals” passivelyexpand/collapse when extended out from/drawn in to catheter, and whencollapsed, the tips of the loops extend past the tip of a straightneedle to inhibit gouging the ID of catheter, or tissue when partiallyretracted. In its deployed configuration, the penetrationlimiting/perforation protection system significantly reduces the risk ofperforation with a straight needle system.

A proximal portion 700 of a delivery catheter with two fluid lumens isshown in FIG. 7 and includes a handle assembly 701 attached to a maincatheter shaft 705 by a strain relief assembly 703. The catheter shaft705 is a flexible, torquable composite conduit for the therapy andcontrast delivery lumens. The strain relief assembly 703 serves as aprotective transition between the catheter shaft and the handle assembly701. Although the helical needle systems of the present invention mayhave a lower likelihood of perforation than the straight needleembodiments, there may be advantages to including such a perforationprotection embodiment to a helical needle catheter which can be readilyimplemented.

FIG. 8A (panels 1-4) illustrates a penetration limiting/perorationprotection including exemplary leaflet or petal elements. The leafletelements 801 can be independent as shown above, or can have connectedlegs in what we would call a “monolithic structure” 806, e.g. allleaflets or petals may be formed from a single length of Nitinol® orother shape memory metal or polymer, where the length is furtheroptionally connected at the ends to form a continuous structure withmultiple loops. The legs can be of straight or have some otherconvoluted shape to improve bonding in an adhesive junction. The loopshave several radii which aid in the collapse and/or expansion of thestructure during sheathing and deployment. A major diameter 801 aprimarily defines the sheathed length relative to the needle which iscovered and protected. The “folding blip” 801 b is designed to preventplastic strain upon sheathing where that segment of geometry is folded180 degrees. The “root” radii 801 d make sheathing easier, as the leverarm for folding down the leaflet is increased when this radius isincreased. Radiopacity can be provided by covering the leaflets withcoiled platinum 801 e as shown in FIG. 8B (panel 1), or made from drawnfilled tube (DFT) with a radiopaque center such as platinum 801 f asshown FIG. 8B (panel 2). Radiopacity coils can be attached withgeometric binding, solder, or glue Panel 3 and 4 of FIG. 8B show theloops are made by heat setting on a mandrel which has features to createthe various chosen radii for example 809, 811, and 813.

FIG. 8C shows the dual lumen tube. The dual lumen 803 b (panel 2) has achannel for therapeutic and a channel for contrast. The therapeutic pathis connected to the injection element 808 and delivers agents into thetissue. The contrast lumen opens at the tip of the shaft 805, andcontrast is injected through it to assure correct positioning againstthe tissue surface. Options for the dual lumen include a non-roundextrusion 803 b with recesses for the legs of the leaflets optimizingcross sectional flow area, or a round extrusion could be blow molded tofit around the legs of the leaflets 803 c (panel 3), again optimizingflow area, and also potentially improving leaflet security in bonding tothe shaft. Tissue engagement indicators can provide additionalfeature/benefit of a radiopaque loop is the possibility of having it actas a tissue engagement indicator. Since the tips of the wire loops maybe shaped as to “lead” the tip of the catheter by some distance, as theneedle punctures the tissue and the distal end of the body of thecatheter approaches the tissue surface, the tips of the loops bendingback can be visualized under fluoroscopy. A potential added benefit ofusing the loops to indicate tissue engagement is the possibility ofbeing able to eliminate the contrast lumen from the shaft, which couldenable overall system size reduction or accommodate larger therapeuticlumens which enable the delivery of larger cells, cell aggregates,microspheres, Extra Cellular Matrix (ECM) slurries, particles, or higherviscosity therapeutic agents. The loops could be configured such thatthey form a generally conical shape, a flared bell shape like a trumpet,or closing bell shape like a toilet plunger.

FIG. 8D shows the distal flexible element and needle. The pentafilarcoil 807 is a five element coil of 0.008″ wire with a pitch of 0.046″.This flexible element could optionally be comprised of a cut metal tube807 b (FIG. 8C), which may have the advantages of thinner wall, andvariable flexibility along its length, which if stiffer at the moreproximal region, could improve column support thus improving ability topenetrate tough tissue at long extensions out of the steering deliveryguiding catheter. The shaft typically comprises three main including thehighly flexible distal segment 807, the main length of the shaft 815 andthe strain relief segment 817. Note, the following items are alsoreferenced in FIG. 7 as the main shaft, 705, and strain relief, 703.

The flexible element is as previously mentioned, may be fabricated of afive filar coil of stainless steel round wire 807. The main shaft iscomprised of the outer jacket (braided polyamide) 815, and the innerdual lumen (Pebax) 803 (FIG. 8A). The strain relief 817 contains anextension of the main shaft and dual lumen 815 and also has two segmentsof PEEK, one smaller 817 a which fits inside the handle of the guidingcatheter, and one larger 817 b which can enter a rotating hemostasisvalve (RHV) attached to the proximal luer of the guide catheter, butwhich does not enter the handle of the guide. The step at the end of thelarger OD between the two strain relief sections is used as a referencepoint touched by the user to assess that the distal tip is just“garaged” within the guiding catheter while that junction is just at theproximal edge of the RHV.

Optionally, an introducer sheath can be slidably attached to the handle,shaft along the shaft, and cause the leaflets to fold forward forintroduction into the guiding catheter. This element can become part ofthe strain relief, e.g. a snap fit design 817 c (panel 1, FIG. 8E). Thejunction between the main shaft segment 815 and the distal flexibleelement 807 is formed with a thin walled hypotube or “bushing” bonded inplace with cyanoacrylate adhesive. The junctions from the main shaft 815to the strain relief 817 and the strain relief to the handle 819 may bemade by epoxy adhesive, reference FIG. 8D.

Wire assemblies, e.g. 801 and 806 of FIG. 8A, may be pre-tinned withAu—Sn solder, then soldered to a stainless steel needle & coil (or otherflexible spring element) as a subassembly for simplification ofmanufacture. The radius of curvature of the wire as it leaves itsattachment point should not be smaller than 10 times the wire diameter.Smallest recommended ratio is approximately 5.6:1, but that will likelyplastically deform with use and have reduced fatigue life. Monolithicset of wire loops provide for ease of assembly, for consistency oflongitudinal and radial spacing, and for increased security inattachment as opposed to single individual leaflets with straight“legs”).

FIG. 8D shows the distal flexible element and needle in including apentafiler coil 807 which is a five element coil of 0.008″ wire with apitch of 0.046″. This flexible element could optionally be comprised ofa cut metal tube 807 b (FIG. 8C), which may have the advantages ofthinner wall, and variable flexibility along its length, which ifstiffer at the more proximal region, could improve column support thusimproving ability to penetrate tough tissue at long extensions out ofthe steering delivery guiding catheter. The shaft 807, 815, and 817includes three main segments (FIG. 8D): the highly flexible distalsegment 807, the main length of the shaft 815, and the strain reliefsegment 817.

The therapeutic lumen and contrast lumen will typically rununinterrupted the full length of catheter shaft. A junction between thepentafiler coil 807 and the polyamide jacket 815 is formed with anadhesive lap joint. This has been formed by Loctite 4014 bonding toeither a thin walled 304 stainless bushing, not shown, with an ID/OD0.038″/0.042″×0.3″ long, or using the outer surface of the lumenassembly as the lap joint material. Proximal to the coil-shaft junction,the main shaft outer jacket is a flexible torquable composite comprisedof an 0.042″ ID by 0.054″ OD polyamide tube with 0.0015″ wire braid (16carrier) encapsulated in the wall 815.

The strain relief assembly 703 serves as a protective transition betweenthe catheter shaft and the handle assembly 701. As shown in FIG. 8D, thestrain relief 81 contains an extension of the main shaft and dual lumen815 and also has two segments of PEEK, one smaller (0.062″ ID×0.010″wall) 817 a which fits inside the handle of the guiding catheter, andone larger (0.085″ ID×0.010″ wall) 817 b which can enter a rotatinghemostasis valve (RHV) 1902 attached to the proximal luer of the guidecatheter 1901, but which does not enter the handle of the guide. Thestep between the two OD's can be used as a reference point, touched bythe user to assess that the distal tip is just “garaged” within theguiding catheter while that junction is just at the proximal edge of theRHV without having to expose the patient to increased radiation by usingfluoroscopy to verify needle tip position.

FIG. 8F, panels 1 and 2, shows that in cases where packing may beslightly too tight, the loops at the tip take up more space than themain body of the loop, so the tip positioning (in collapsed state) maybe staggered axially (panel 2) either by staggering the root position,or by having differing loop sizes. The leaflets may be made so that theyare self-reinforcing in a deployed configuration to reduce ease of foldback. One approach is for each loop threaded through an adjacent loop asshown. Another variation shown is a “steam colander” variation 801 h(panels 3-6), with flexible sheets, or plates in curved triangularsegments of conical section. Optionally the edges can have a folding orsliding interlocking mechanism to limit “splay” 801 i.

FIG. 9 is a cross sectional view of the handle assembly 701 from FIG. 7which can be standard for many of the dual lumen catheters here. Thehandle is an ergonomic catheter control feature containing the proximalports of both the therapy and contrast lumens 901, 903. The cathetershaft 805 is secured directly to the strain relief assembly using epoxyadhesive such as Loctite M-06FL. A retaining block 913 is used tointegrate the strain relief assembly and catheter shaft with the handleassembly using Loctite 4013 cyanoacrylate adhesive. Inside the handleassembly the catheter shaft 911 terminates just proximal to theretaining block.

At the main shaft termination, the contrast lumen 907 is isolated anddirected toward the contrast proximal luer 901. At the catheter shafttermination, 911, the therapy lumen is also isolated and a bushing, 909,is used to connect an extension tube, 905, to the therapy lumen in themain shaft. The proximal end of the extension tube is connected to thetherapy proximal luer, 903.

An alternative version of terminating the contrast and therapeuticlumens utilizes a “Y” adapter 2201, as illustrated in FIG. 22, allowingconcentric therapy lumen 2202 and contrast lumen 2203 tubingconfigurations to be adhesively bonded directly to the “Y” adapter whichterminates in luer-lock fitting for the therapeutic and contrastinjection ports 901 & 903.

Current commercial trans-endocardial infusion system uses a helicalneedle made from 27RW gage 304 stainless steel hypotube (ID=0.008″). Thedesire to pass larger sized entities led to the development of largerhelical wound hypotubes. Material and design constraints (functionalrequirements) were used to optimize the helix parameters of pitch, helixID, helix OD, hypotube ID and hypo tube wall thickness. Various formingtechniques were used to further optimize acceptably formed needles; forexample, to control ovalization of the hypotube inside diameter. FIGS.10 through 12 show the distal tip of a three lumen catheter with a twolumen delivery needle 1130 a contrast lumen that terminates at the baseof the needle, 1120, and the flexible distal element 1110 a pentifilarcoil component. All of these features are secured together as the distaltip 1140 as shown using a two part epoxy as the bonding material. Thepreferred embodiment for the Helix Plus needle element is a helicalshaped, dual stainless steel hypotube structure 1130. For the preferredembodiment, the proximal end of both hypotubes are bonded to independenttubes 1210, that serve as the axial conduit for fluid transport.Alternate embodiments include a lumen-in-lumen design 1150 which hasbeen described previously by Miller in U.S. Pat. No. 7,736,346. Thehelical needle, 1130 also serves as the distal electrode forelectrophysiological sensing capabilities connected via electrode wire12, and the exposed flexible distal element serves as the returnelectrode also connected by wire not shown.

FIG. 13 shows a cross section of this tri-lumen configuration, 1340,that runs the distance of the device to the handle (electrode wires notshown). The distal and proximal electrode wires also run the length ofthe catheter with the tri-lumen bundle 1310 from their distal attachmentpoints to the handle.

FIG. 14 shows the electrical connections of this system in more detail.The preferred design for the proximal sensing electrode to uses thedistal flexible element formed of exposed pentafiler coil 1110 as theproximal electrode. An electrode wire 1410 is attached to the proximalend of the flexible element. One method of wire attachment is achievedby feeding the electrode wire through the attachment bushing 1405winding the wire into the flexible element, 1440, and then soldered inplace 1420. An alternate second electrode design uses a conductiveproximal ring 1430 with the electrode wire being directed through theflexible element and attached to the ring.

FIG. 15 shows the internal configuration for the Helix Plus handleassembly. The following describes the proximal termination within thehandle 1610 for the three liquid carrying lumens and the two electrodewires. A multi-channel electrical connector 1630 is integrated into thehandle with both electrodes 1620 being connected to the component withinthe handle. The three lumens used for the preferred tri-lumen design areall contained within the catheter shaft, 1030 continue through thestrain relief assembly 1040 and exit within the handle assembly. Theindividual lumens are then directed to a proximal port in the handle1140 where they exit and connect to standard luer fittings.

FIGS. 16 and 17 shows a large bore needle based on 23 Ga tubing 1700,and a 27RW gage helical needle 1750. The needle is secured into the tipassembly by first using UV adhesive such as Loctite 3301 to bond it intothe therapeutic lumen, then secondly embedding the needle andtherapeutic lumen into the pentafiler coil using in an epoxy such asLoctite M-31CL to form a unibody structure 1720 that captures a loop ofthe Helix. During the distal epoxy encapsulation a ribbon of PTFE is fedbetween the coiled loops of the needle and into the contrast lumen(adjacent to, or concentrically around the therapeutic lumen) and thisPTFE ribbon creates a flow path through the epoxy when it is removedafter the epoxy has cured. This contrast lumen terminates at the distalend of the embedment at the base of the exposed needle 1730. Thecontrast lumen can be used to assess that the tip of the shaft 805 ispositioned firmly against the myocardium when a needle is screwed intotissue. This assessment is performed by injecting contrast and observingon x-ray the resulting flow and how it pools and hangs with a boundarylayer against the myocardium, or if it simply flows away like a puff ofsmoke with the flow of the cardiac pumping.

FIG. 18 shows an alternate design for distal perforation protectionutilizing existing balloon technology when engaging heart tissue duringtrans-endocardial therapy delivery. FIG. 18 shows three different viewsfor the distally attached balloon feature; side view in the un-inflatedstate 1801 the side view in the inflated state 1802 and an isometricview of the inflated state 1803. A distally attached balloon featureprovides a barrier at the proximal end of the needle 1010, as shown in1802. The preferred deployment would involve inflating the balloon,using saline or contrast medium, after it is exposed from its guidecatheter and before full engagement into the heart wall. To inflate theballoon, fluid is injected in a port attached to the handle that runsthrough an internal lumen terminating below the surface of the balloonregion in the distal end. A key advantage for this design is the abilityto have a perforation protection system integrated into the distal endof the helical infusion catheter that is capable of function whenrotated during standard use with a helical needle. Use of contrast asthe balloon inflation medium provides the added benefit of a largeradiopaque volume at the endocardial plane that can further assist withneedle location and engagement assessment. A suitable balloon material,conforming to the catheter distal end in the un-inflated state 1810 isbonded at its distal and proximal ends to the base distal end structure.A port below the balloon structure connects via a suitable conduit to aninflation port in the handle.

A currently available trans-endocardial infusion systems (BioCardia,Inc.) use a helical needle made from 27RW gage 304 stainless steelhypotube (ID=0.008″, OD=0.016″). The desire to use a larger lumenpassing a wider range of therapeutic agents led to the development ofhelical wound needles utilizing larger gage tubing. Material propertiesconstraints and the desire to maintain the smallest profile wereevaluated to optimize helix needle parameters of pitch, helix ID, helixOD, hypotube ID and hypo tube wall thickness. Various forming techniqueswere used to further optimize acceptably formed needles; for example, tocontrol ovalization of the hypotube inside diameter. Mandrel sizes werevaried to control material deformation while trying to maintain helixdiameter within constraints. Other methods of controlling excessiveovalization included freezing water in the hypotube prior to coiling,annealing the hypotube prior to coiling and side wall support duringwinding.

Commercial tube benders use a general rule of thumb that the bend radiusof the coiled tube should not be less than two times the tube diameter,although using proprietary methods a 1:1 relationship can be achieved.Theoretical limits associated with material elongation were evaluatedbased on 60% elongation=0.5*Tube Diameter(TD)/Bending Radius (RB)wherethe % elongation limit is based on 304SS. The mandrel diameter (MD) is2*RB−TD and the helix diameter is 2*TD+MD.

For example, a 23 gage TW 304SS hypotube with an outer diameter=0.025inhas a theoretical minimum bend radius at 60% elongation of 0.021in(RB=(0.5*TB)/0.6). The resultant theoretical minimum mandrel diameter is0.019 in with a helix diameter of 0.069 in. Experimental results variedfrom this theory as hypotubes tended to fail via ovalization versustensile failure and the wound helix experienced “spring back” such thatthe final helix diameter was larger than theory.

The mandrel used to make the 23 gage TW Large Bore needles was specifiedto have a minor diameter of 0.018±0.002″ and produced a helix outerdiameter ranging from 0.071 in to 0.074 in with an inner diameter ofapproximately 0.024 in. The “spring back” and ovalization experienced bythe helix is thusly documented and demonstrates that 23Ga TW helicalneedles wound on the Φ0.018″ mandrel can feasibly meet an outer diametermaximum specification.

FIG. 19 shows an assembled system consisting of the following a Morph895 deflectable tip catheter 1901 with an attached RHV (Merit MAP150)1902, a syringe attached to the side port of the RHV 1903, a Helixcatheter 1904, a syringe attached to the therapeutic port 1905, and asyringe attached to the contrast port 1906. A Helix needle at the tip1907 is advanced and retracted through the guide to extend past thedeflectable tip of the guide 1908 controlled by a guide deflection knob1909.

FIG. 20 shows a Helix catheter consisting of the Helical needle 1907,the flexible distal element 2001, the braided shaft 2002, the two partstrain relief 2003, the handle 2004, the therapeutic port 903 and thecontrast port 901.

FIGS. 21A through 21D show one method of Helix needle forming wrappinghypotube onto a mandrel 2001 which supports the sides of the tube toreduce ovalization.

The needle can be formed with a variety of sized hypodermic tubing, Thecurrent commercially available iteration is made from 27GA RW 304stainless steel. Large bore versions have been built using 24 and 23Gatubing. Preferred stainless steel embodiments conform to ISO 9626 AnnexA & E. Additional methods and materials to overcome limitations ofmaterial cold work limits may include forming directly to shape withelectroforming of nickel or other material over a chemically removablewound mandrel such as aluminum or copper. After winding, the primaryfacet is cut 2002, then the secondary facets are added 2003. Additionaloption may include alternative tips such as closed form with side holes,trocar, or Tuohy tips. In preferred embodiments the final formed needlehas a straight tail 2004 which is offset from center by an amount equalto the lumen offset in the shaft assembly, and which is bonded into thetherapeutic lumen.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention, which is defined by the appendedclaims.

What is claimed is:
 1. A method for introducing a needle injectioncatheter into a heart chamber from a radial artery, said methodcomprising: advancing a guide catheter through the radial artery andinto the heart chamber; positioning the guide catheter to align a distaltip of the guide catheter with a target location on an endocardial wallof the heart chamber; advancing the needle-injection catheter through alumen of the guide catheter so that a straight needle projectingcoaxially emerges from a distal tip of the needle injection catheter andpenetrates the endocardial wall to position an injection port at the tipof the needle in the myocardium, wherein a plurality of penetrationlimiting elements remain constrained within the guide catheter until theneedle emerges from the distal tip at which point the elementsself-deploy radially outwardly from a base of the needle to limit thepenetration of the needle into the myocardium in order to reduce therisk of perforation of the endocardial wall.
 2. A method as in claim 1,wherein positioning comprises rotating and/or axially translating aguide catheter having a pre-shaped deflection at its distal end.
 3. Amethod as in claim 1, wherein positioning comprises deflecting thedistal tip of the guide catheter while the guide catheter is in theheart chamber.
 4. A method as in claim 1, wherein advancing theneedle-injection catheter comprises constraining the penetrationlimiting elements in an introducer sleeve, engaging a distal end of thesleeve against a proximal hub of the guide catheter, and advancing adistal end of the needle-injection catheter into a proximal portion ofthe guide catheter while the penetration limiting elements remainconstrained.
 5. A method as in claim 1, wherein the penetration limitingelements comprise resilient petals which have bases attached to thecatheter body at the base of the straight needle.
 6. A method as inclaim 5, wherein the petals are shaped to curve outwardly from thecatheter body when unconstrained.
 7. A method as in claim 6, wherein thepetals are wire loops folded in a continuous length of a shape memorywire.
 8. A method as in claim 7, wherein a platinum wire is wound overthe shape memory wire to provide radiopacity.
 9. A method as in claim 6,wherein the petals are solid leaves which overlap when folded inwardlyagainst the needle shaft.
 10. A method as in claim 5, wherein thecatheter includes from two to six petals.
 11. A needle-injectioncatheter comprising: a catheter body having a distal end, a proximalend, a stiff proximal portion, a flexible distal portion, and a deliverylumen extending therethrough; a straight injection needle extendingcoaxially from a distal tip of the flexible portion of the catheterbody; and a plurality of penetration limiting elements positionedcircumferentially about a base of the straight injection needle andconfigured to fold radially inwardly against a shaft of the needle whenconstrained in a tubular lumen and to extend radially outwardly whenunconstrained.
 12. A catheter as in claim 11, wherein the penetrationlimiting elements comprise resilient petals which have bases attached tothe catheter body at the base of the straight needle.
 13. A catheter asin claim 12, wherein the petals are shaped to curve outwardly from thecatheter body when unconstrained.
 14. A catheter as in claim 13, whereinthe petals are wire loops folded in a continuous length of a shapememory wire.
 15. A catheter as in claim 14, wherein a platinum wire iswound over the shape memory wire to provide radiopacity.
 16. A catheteras in claim 13, wherein the petals are solid leaves which overlap whenfolded inwardly against the needle shaft.
 17. A catheter as in claim 12,wherein the catheter includes from two to six petals.
 18. A catheter asin claim 11, wherein the stiff proximal portion of the catheter bodycomprises a braided polymeric tube and the flexible distal portion ofthe catheter body comprises a helical metal coil.
 19. A catheter as inclaim 11, wherein the catheter body has a first lumen for delivering aninjectable composition to the needle and a second lumen for delivery ofa contrast agent to the base of the needle.
 20. A catheter as in claim11, further comprising a handle on the proximal end of the catheterbody.
 21. A catheter as in claim 11, wherein the catheter body isconfigured to be delivered through a 6.5 Fr guide catheter.
 22. Acatheter system comprising: a needle-injection catheter as in claim 11,and a guide catheter having a lumen configured to receive theneedle-injection catheter and to radially constrain the plurality ofpenetration limiting elements when the needle-injection catheter istherein.
 23. A catheter system as in claim 22, wherein the guidecatheter has a pre-shaped bend near its distal end so that the guidecatheter can be rotated to align the distal end with a target locationon an endocardial wall when the guide catheter is in a heart chamber.24. A catheter system as in claim 22, wherein the guide catheter has adeflectable distal end to align the distal end with a target location onan endocardial wall when the guide catheter is in a heart chamber.
 25. Alarge-bore needle injection catheter comprising: a catheter body havinga distal end, a proximal end, and a delivery lumen therethrough; ahelical needle extending from the distal end of the catheter body andhaving at least one helical delivery lumen connected to receive aninjectable substance from the delivery lumen of the catheter body,wherein the delivery lumen and the at least one helical lumen aresufficiently large to permit the passage and injection of drugs orbiological materials having a mean diameter of at least 50 μm.
 26. Acatheter as in claim 25, wherein the delivery lumen has a diameter of atleast 0.5 mm.
 27. A catheter as in claim 26, wherein the helical lumenhas a diameter of at least 0.2 mm.
 28. A catheter as in claim 27,wherein the catheter body has at least one lumen in addition to thedelivery lumen and the helical needle has at least two helical deliverylumens with one connected to at least the each of the catheter bodylumens.
 29. A catheter as in claim 25, wherein the catheter bodycomprises a stiff proximal portion and a flexible distal portion.
 30. Acatheter as in claim 27, wherein the stiff proximal portion of thecatheter body comprises a braided polymeric tube and the flexible distalportion of the catheter body comprises a helical metal coil.
 31. Acatheter as in claim 25, wherein the catheter body a first lumen fordelivery of an injectable composition to the needle and a second lumenfor delivery of a contrast agent to the base of the needle.
 32. Acatheter as in claim 25, further comprising a handle on the proximal endof the catheter body.
 33. A catheter system comprising: a large-boreneedle catheter as in claim 25; and a guide catheter having a lumenconfigured to receive the large-bore needle catheter.
 34. A cathetersystem as in claim 33, wherein the guide catheter has a pre-shaped bendnear its distal end so that the guide catheter can be rotated to alignthe distal end with a target location on an endocardial wall when theguide catheter is in a heart chamber.
 35. A catheter system as in claim33, wherein the guide catheter has a deflectable distal end to align thedistal end with a target location on an endocardial wall when the guidecatheter is in a heart chamber.
 36. A method for delivering aparticulate material into an endocardial wall of a heart chamber, of abeating heart, said method comprising: intravascularly introducing alarge bore needle injection catheter having a helical needle into aheart chamber; rotationally advancing the helical needle of the largebore needle injection catheter into an endocardial wall of the heartchamber so that a port on the needle lies near an interior end of ahelical tissue tract formed by the needle; injecting a particulatematerial having a mean particle diameter of at least 50 μm through theneedle into the interior end of the helical tissue tract wherein flowback of the injected material through the helical tissue tract isinhibited in the helical shape of the tract even after the helicalneedle is withdrawn.
 37. A method as in claims 36, wherein the catheterhas a catheter body with a delivery lumen has a diameter of at least 0.5mm.
 38. A catheter as in claim 37, wherein the helical needle has ahelical lumen with a diameter of at least 0.2 mm.
 39. A catheter as inclaim 38, wherein the catheter body has at least one lumen in additionto the delivery lumen and the helical needle has at least two helicaldelivery lumens with one connected to at least the each of the catheterbody lumens.